Endocrine therapy trials of aromatase inhibitors for breast cancer in the adjuvant and prevention settings

James N. Ingle, Stephen Johnston, Kent Osborne, Steven Come, Per Lønning, Richard Santen, Aman Buzdar

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Abstract

The recent past has witnessed the appearance of substantial data relating to endocrine therapy of breast cancer. In the adjuvant therapy setting in early breast cancer, several large, well-conducted, randomized, double-blind clinical trials have provided evidence for the value of the third-generation aromatase inhibitors (AI) anastrozole, exemestame, and letrozole. The three major studies to date [i.e., Arimidex, tamoxifen alone, or in combination (ATAC), International Exemestane Study (IES), and letrozole after 5 years of tamoxifen (MA. 17)] evaluated three different populations of women from the standpoints of duration of prior tamoxifen and thus time since the treatment of the primary breast cancer. A consistent pattern of improvement in disease-free survival was seen whether the control arm was tamoxifen (ATAC and IES) or placebo following tamoxifen (MA.17). From a toxicity standpoint, the major findings with the AIs were a decreased incidence of thromboembolic events and endometrial cancers but an increase in mosculoskeletal complaints and potential for decreasing bone density. The last issue should be clarified with ongoing studies addressing the impact of the three AIs on bone density and fractures. In summary, based on ATAC, IES, and MA.17, respectively, the following conclusions can be drawn relating to postmenopausal women with hormone receptor positive early breast cancer: anastrozole is a reasonable choice for initial endocrine adjuvant therapy, exemestane should be considered for women who have received 2 to 3 years of tamoxifen, and letrozole should be considered for those who have completed about 5 years of tamoxifen. In the prevention setting, tamoxifen has been evaluated in multiple trials involving >28,000 women and, despite clear evidence of benefit, the level of acceptance of this agent by women seems to be low. Two recently developed prevention trials, IBIS 2 and MAP.3, involve the study of aromatase inhibitors against a placebo control rather than tamoxifen. Whereas the recent adjuvant trials have established the value of the third-generation aromatase inhibitors in early-stage breast cancer, the marked reductions in contralateral breast cancers seen in these trials suggest they will be of value in the prevention setting in women at increased risk of developing the disease.

Original languageEnglish (US)
JournalClinical Cancer Research
Volume11
Issue number2 II
StatePublished - Jan 15 2005

Fingerprint

Aromatase Inhibitors
Tamoxifen
exemestane
Breast Neoplasms
letrozole
Therapeutics
Bone Density
Placebos
Bone Fractures
Endometrial Neoplasms
Disease-Free Survival
anastrozole
Clinical Trials
Hormones

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ingle, J. N., Johnston, S., Osborne, K., Come, S., Lønning, P., Santen, R., & Buzdar, A. (2005). Endocrine therapy trials of aromatase inhibitors for breast cancer in the adjuvant and prevention settings. Clinical Cancer Research, 11(2 II).

Endocrine therapy trials of aromatase inhibitors for breast cancer in the adjuvant and prevention settings. / Ingle, James N.; Johnston, Stephen; Osborne, Kent; Come, Steven; Lønning, Per; Santen, Richard; Buzdar, Aman.

In: Clinical Cancer Research, Vol. 11, No. 2 II, 15.01.2005.

Research output: Contribution to journalArticle

Ingle, JN, Johnston, S, Osborne, K, Come, S, Lønning, P, Santen, R & Buzdar, A 2005, 'Endocrine therapy trials of aromatase inhibitors for breast cancer in the adjuvant and prevention settings', Clinical Cancer Research, vol. 11, no. 2 II.
Ingle JN, Johnston S, Osborne K, Come S, Lønning P, Santen R et al. Endocrine therapy trials of aromatase inhibitors for breast cancer in the adjuvant and prevention settings. Clinical Cancer Research. 2005 Jan 15;11(2 II).
Ingle, James N. ; Johnston, Stephen ; Osborne, Kent ; Come, Steven ; Lønning, Per ; Santen, Richard ; Buzdar, Aman. / Endocrine therapy trials of aromatase inhibitors for breast cancer in the adjuvant and prevention settings. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 2 II.
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